人类性结肠炎表皮的体质炎症基因突变
Kosaku Nanki1,2, Masayuki Fujii1,3, Mariko Shimokawa1
1Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
Nature
|December 20, 2019
概括
衰老的组织会积累癌症突变. 在性结肠炎患者中,结肠细胞在IL-17信号基因中发生突变,可能导致炎症和疾病.
科学领域:
- 胃肠病学
- 遗传学
- 免疫学
背景情况:
- 衰老的组织积累了癌症突变的体质克隆.
- 在非新发性人类肠道中的克隆扩张尚未得到充分了解.
- 性结肠炎是一种慢性肠炎症.
研究的目的:
- 在性结肠炎患者的结肠表皮中研究体质突变.
- 确定炎症结肠中的突变是否具有功能优势.
- 探索体质突变与性结肠炎的发生之间的联系.
主要方法:
- 76个人类结肠器官的全外体测序.
- 针对性测序以验证突变的传播.
- 在结肠器官中基于CRISPR的淘汰查.
主要成果:
- 在性结肠炎上发现了一种独特的突变模式.
- 在IL-17信号通路基因 (NFKBIZ,ZC3H12A,PIGR) 中发现了突变.
- 突变使结肠器官对IL-17A诱导的亡产生抗性.
结论:
- 人体结肠上皮的体质突变与炎症有关.
- 突变可能促进性结肠炎的敌对微环境中的生存.
- 这种基因适应可能会导致性结肠炎的发病.
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